Very little is known about the genetic alterations contributing o the development and progression of oral cancer. Currently, there are no large scale genomic studies addressing these issues, presumably owing to the cost and difficulties associated with such efforts. Yet knowledge of the underlying genetic causes of oral cancer is crucial to the design of targeted therapies and identification of molecular markers that may prove valuable in the prognosis or early detection. The overall objective of this research proposal is to generate a comprehensive database of the genomic alterations in oral cancer. Leveraging the strength of our extensive and well annotated tumor tissue bank at the University of Texas M.D. Anderson Cancer Center and cutting edge technology developed by Baylor College of Medicine's Human Genome Sequencing Center, we will perform somatic mutation analysis on over 6000 cancer-related genes and identify structural abnormalities over the whole genome for 100 cases of squamous cell carcinoma of the oral tongue (SCCOT). This study will generate information regarding genetic alterations present in SCOTT in unprecedented detail, including mutations, copy number alterations and chromosomal translocations. This single project has widespread potential to result in discovery of dozens of novel therapeutic targets for a cancer where the primary treatments are still surgery, chemotherapy and radiation. Moreover, identification of a panel of genes specifically altered in oral cancer is a critical step in developing diagnostic tests for personalized medicine to treat these devastating and often fatal cancers. At the conclusion of this study, SCCOT will be one of the most well characterized tumor types on the genomic level. PUBLIC HEALTH RELEVANCE: Oral cancer affects 300,000 persons worldwide each year, and the overall survival rate is just above 50%. All cancers are genetic diseases and a better understanding of the genetic alterations that cause cancer could be used to design more effective tumor-specific therapies. This study is a comprehensive large-scale examination of all the genetic changes found in tumors derived from patients with oral cancer and the information gained could have a major impact on the way we treat and detect these and other cancers.